The goal of this project is to identify the mechanisms by which transcription factors of the Helix-loop-helix class control proliferation and differentiaton during development, and to identify mechanisms that might be used to influence such proteins in diseases. Studies of eye development in Drosophila melanogaster have identified a conserved common mechanism that regulates photoreceptor cell differentiation and also functions in many other organs. The molecular mechanisms that regulate helix-loop-helix proteins in the eye and other tissues will be elucidated through molecular genetic studies of transcriptional, post-transcriptional, and post-translational regulation. The connection between differentiation and cell proliferation and survival will be elucidated from studies of the regulatin of tumor suppressor genes by helix-loop-helix transcription factors. Genetic screens will be conducted that will identify other components of the process, and seek to identify novel molecular mechanisms by which disease processes can be influenced.